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. 2011 Jun;24(2):95-111.
doi: 10.1293/tox.24.95. Epub 2011 Jun 30.

Toxicological pathology in the rat placenta

Satoshi Furukawa  1 , Seigo Hayashi, Koji Usuda, Masayoshi Abe, Soichiro Hagio, Izumi Ogawa
Affiliations

Toxicological pathology in the rat placenta

Satoshi Furukawa et al. J Toxicol Pathol. 2011 Jun.

Abstract

The placenta grows rapidly for a short period with high blood flow during pregnancy and has multifaceted functions, such as its barrier function, nutritional transport, drug metabolizing activity and endocrine action. Consequently, the placenta is a highly susceptible target organ for drug- or chemical-induced adverse effects, and many placenta-toxic agents have been reported. However, histopathological examination of the placenta is not generally performed, and the placental toxicity index is only the placental weight change in rat reproductive toxicity studies. The placental cells originate from the trophectoderm of the embryo and the endometrium of the dam, proliferate and differentiate into a variety of tissues with interaction each other according to the development sequence, resulting in formation of a placenta. Therefore, drug- or chemical-induced placental lesions show various histopathological features depending on the toxicants and the exposure period, and the pathogenesis of placental toxicity is complicated. Placental weight assessment appears not to be enough to evaluate placental toxicity, and reproductive toxicity studies should pay more attention to histopathological evaluation of placental tissue. The detailed histopathological approaches to investigation of the pathogenesis of placental toxicity are considered to provide an important tool for understanding the mechanism of teratogenicity and developmental toxicity with embryo lethality, and could benefit reproductive toxicity studies.

Keywords: placental hypertrophy; placental pathology; rat; small placenta.

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Figures

Fig.1.
Fig.1.
Placental classification of chorioallantoic placentas according to the relationship established between the chorion and uterine wall. The remaining fetal components include three layers (trophoblast, basement membrane and fetal capillary), whereas the maternal components are reduced step by step. BM, basement membrane; CE, chorionic epithelium (trophoblasts); Cy, cytotrophoblast; FB, fetal blood; FC, fetal capillary; MB, maternal blood; MC, maternal capillary; MI, maternal interstitium; Sy, syncytio trophoblast;UE,uterineepithelium.(Figuremodifiedfrom that of Burton et al.6)
Fig. 2.
Fig. 2.
Structural components and differentiation of the rat placenta.
Fig. 3.
Fig. 3.
Rat embryo and placenta. (Left - GD 7, right - GD 9, HE stain) AC, amniotic cavity; AL, allantois; AM, amnion; CH, chorion; ECT, ectoplacental cavity; EPC, ectoplacental cone; EX, extraembryonic coelom; PAC, proamniotic cavity; PDZ, primary decidual zone; SDZ, secondary decidual zone; T, trophectoderm; YC, yolk sac cavity.
Fig. 4.
Fig. 4.
Rat embryo and placenta (GD 10, HE stain). AC, amniotic cavity; AL, allantois; AM, amnion; CH, chorion; Em, embryo; EPC, ectoplacental cone; EX, extraembryonic coelom; FG, foregut pocket; HG, hindgut pocket; PYS, parietal layer of yolk sac; VYS, visceral layer of yolk sac.
Fig. 5.
Fig. 5.
Placental development schema (Left - rat; right - rabbit). Black area shows the fetal part of the placenta. (Figure modified from those of Davies et al.8 and Hafez et al.9.)
Fig. 6.
Fig. 6.
Rat placenta (GD 15, HE stain, lower left, low magnification; lower right, decidua basalis; higher left, yolk sac; higher middle, labyrinth zone; higher right, basal zone). B, basal zone; DB, decidua basalis; FC, fetal capillary; G, trophoblastic giant cell; GlyC, glycogen cell; L, labyrinth zone; MG, metrial gland; MS, maternal sinusoid; NKC, uterine natural killer cells; ST, spongiotrophoblast; T, trophoblast; YS, yolk sac.
Fig. 7.
Fig. 7.
Rat placental ultrastructure (GD 17). Cy, cytotrophoblast; FB, fetal blood; FC, fetal capillary; MB, maternal blood; MS, maternal sinusoid; Sy, syncytiotrophoblast.
Fig. 8.
Fig. 8.
Time-dependent change in the thickness of each placental layer in the rat.
Fig. 9.
Fig. 9.
Placental circulation in the rat.
Fig. 10.
Fig. 10.
Placental comparison between the rat and human.
Fig. 11.
Fig. 11.
Time-dependent change in placental and fetal weight in the rat.
Fig. 12.
Fig. 12.
Placental hypertrophy (Rat, GD 21, left - control; right - ketoconazole). Ketoconazole treatment.
Fig. 13.
Fig. 13.
Thickening of the basal zone (Rat, GD 17, HE stain, left - control; right - ketoconazole). Ketoconazole treatment. B, basal zone; DB, decidua basalis; GlyC, glycogen cell; L, labyrinth zone; ST, spongiotrophoblast.
Fig. 14.
Fig. 14.
Placental necrosis. Discoloration of the placenta and adherence of the yolk sac to the chorionic surface (Rat, GD 19). Cadmium chloride treatment.
Fig. 15.
Fig. 15.
Calcificationandirregulardilatationofthematernalsinusoid in the labyrinth zone (Rat, GD 21, HE stain). Lead acetate treatment.
Fig. 16.
Fig. 16.
Left - extensive necrosis in the labyrinth zone (Rat, GD 19, HE stain). Right - expression of metallothionein in cad-mium-damaged trophoblasts in the labyrinth zone (Rat, GD 19, metallothionein immunostain). Cadmium chloride treatment.
Fig. 17.
Fig. 17.
Iron deposition in fetal erythroblasts and trophoblastic septa in the labyrinth zone (Rat, GD 13, Berlin blue stain). Compound A treatment.
Fig. 18.
Fig. 18.
Thickening of the basal zone with cytolysis of glycogen cells(↑)(Rat, GD21, HE stain). Treatment with 6-MP.
Fig. 19.
Fig. 19.
Small placenta (Rat, GD 21, left - control; right - busulfan). Busulfan treatment.
Fig. 20.
Fig. 20.
Left - apoptosis of trophoblasts in the labyrinth zone (Rat, GD 15, TUNEL stain). Right - degeneration and necrosis of trophoblasts with deposition of calcium in the labyrinth zone (Rat, GD 21, HE stain). Busulfan treatment.
Fig. 21.
Fig. 21.
Small placenta (Rat, GD 21, left - control; right - 6-MP). Treatment with 6-MP.
Fig. 22.
Fig. 22.
Left - Apoptosis of trophoblasts in the labyrinth zone (Rat, GD 13, HE stain). Right - decreased number of trophoblasts, a reduction in thickness of trophoblastic septa and irregular dilatation of maternal sinusoids with deposition of fibrin (Rat, GD21, HE stain). Treatment with 6-MP.
Fig. 23.
Fig. 23.
Increased PAS-positive material in spongiotrophoblasts around clusters of glycogen cells (Rat, GD 15, PAS stain, left - control; right - 6-MP). Treatment with 6-MP.
Fig. 24.
Fig. 24.
Apoptosis of spongiotrophoblasts in the basal zone (Rat, GD 15, TUNEL stain). Cisplatin treatment.
Fig. 25.
Fig. 25.
Basal zone hypoplasia (Rat, GD 21, HE stain, left - control; right - cisplatin). Cisplatin treatment. B, basal zone; DB, decidua basalis; L, labyrinth zone.
Fig. 26.
Fig. 26.
Decrease in glycogen cell islands and inhibition of interstitial invasion of glycogen cell-like trophoblasts into metrial glands (Rat, GD 15, HE stain, left - control; right - cisplatin). Cisplatin treatment. AC, arterial canal; B, basal zone; D, decidua basalis; GlyC, glycogen cell; L, labyrinth zone; M, metrial gland.
Fig. 27.
Fig. 27.
Metrial gland hypoplasia (Rat, GD 21, HE stain, left - control; right - cisplatin). Cisplatin treatment. MG, metrial gland.
Fig. 28.
Fig. 28.
Marked metrial gland hypoplasia with less well development of spiral arteries (Rat, GD 11, HE stain, left - control; right - tamoxifen). Tamoxifen treatment. DB, decidua basalis; MG, metrial gland.
Fig. 29.
Fig. 29.
Decrease in uNK cells with clear cytoplasm and PAS-positive granules around spiral arteries (Rat, GD 13, PAS stain, left - control; right - tamoxifen). Tamoxifen treatment. SA, spiral artery.
Fig. 30.
Fig. 30.
Vacuolar degeneration of the yolk sac epithelium (Rat, GD 15, HE stain). Trypan blue treatment.
Fig. 31.
Fig. 31.
Increased in expression of GLUT3 (↑) along trophoblastic septa (Rat, GD 17, GLUT3 immunostain, left - control; right - 6MP). Treatment with 6MP.
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